Evaluation of Changes in the Methylome and Prognosis of Obesity-related Breast Cancer After Nutritional Intervention-induced Weight Loss During the Oncological Treatment

Obesity itself is considered the second leading avoidable cause of cancer, after smoking (Renehan and Soerjomataram, 2016;Islami et al., 2019). The worldwide obesity epidemic has shown no signs of abating, better understanding of the mechanisms underlying obesity-associated cancer is urgently needed with the aim to find new therapeutic targets to counteract the obesity-related cancer in general and breast cancer in particular. The increased morbidity and mortality of obesity-related cancer are mostly attributed to dysfunctional adipose tissue. Therefore, targeting the dysfunction of adipose tissue provides a promising strategy for cancer prevention and therapy.

Breast cancer (BC) is the most common female cancer worldwide and the second common cause of cancer-related death in women. In 2018, around 2 million new cases of BC were diagnosed represented 15% of deaths of the 10 most common cancers (Bray et al., 2018). By 2030 cancer is expected to surpass cardiovascular disease being the prevailing cause of death among all age categories, contributing to a 45% increase in the number of malignancies diagnosis during the next 10 years. This is due to the emergence of the increased prevalence of risk factors, mainly diabesity (diabetes mellitus and obesity) in both developed and developing countries (Christodoulatos et al., 2019).

Risk factors for breast cancer include excess weight and metabolic disorders, which have been linked to a poor prognosis of this disease (Bousquenaud et al., 2018;Kliemann et al., 2019;Le et al., 2019). Thus, the World Cancer Research Fund (WCRF) has concluded that healthy lifestyles may help to prevent up to 70% of cancer cases. These include healthy diet eating, regular physical activity, healthy weight, and avoiding smoking and alcohol drinking (Clinton et al., 2019). Obesity is associated with a greater tumor burden in postmenopausal women diagnosed with breast cancer and with a higher degree of tumor. In addition, obesity and overweight are linked to a worse prognosis and an increase in breast cancer death rate. In fact, recently in a work carried out by our research group (Crujeiras et al., 2012), it was found in a homogeneous population in Spain that the prevalence of obesity among breast cancer patients was significantly higher than the prevalence observed among women of the general Spanish population. This increase in prevalence was especially evident in women with postmenopausal breast cancer (Crujeiras et al., 2012). However, although there is epidemiological evidence of the relationship between obesity and cancer, the molecular mechanisms of this relationship is not well known.

Obesity and cancer mechanisms: Adipose tissue secreted factors, inflammation, oxidative stress, epigenetics.

There are several hypothesis that were proposed to be involved in the relationship between obesity and cancer. Among them, the most of the recent studies are being focused on the effect of the dysfunctional adipose tissue observed in obesity (Cabia et al., 2016). Supporting this hypothesis, a recent work of our research group demonstrated that the obese visceral adipose tissue secretome is able to induce higher proliferation of breast tumor cell lines (Crujeiras et al., 2016).